176 Essays in Biochemistry 



deaminations catalyzed by the flavoproteins, L-amino acid oxidase and 

 glycine oxidase, 3 - 4 and indirect oxidative deaminations catalyzed by 

 aminophorases and DPN-dependent glutamic dehydrogenase. 5 Where- 

 as the deaminations brought about by the flavoproteins appear to be 

 irreversible, this is not true of the reactions of the aminophorase — 

 glutamic dehydrogenase system. Indeed with present evidence of the 

 broad scope of transamination reactions 6 it may reasonably be as- 

 sumed that in general the synthesis of amino acids from ammonia and 

 a-keto acids occurs by way of the aminophorase-glutamic dehydro- 

 enase system. Conditions are thus provided for a competition for 

 ammonia between the glutamic dehydrogenase system and step I of 

 the urea cycle, i.e., the citrulline-synthesizing system. This is indi- 

 cated more clearly in the sequence of reactions shown. 



Step II Step I 



T 



Aspartic acid 



DPN+ 



L-Amino acids ;=± Glutamic acid v ^ Ammonia <— L-Amino acids 



DPNH 



In accordance with the fact that the specific enzymatic activity of 

 crystalline beef-liver glutamic dehydrogenase is 10 times greater when 

 the enzyme is present in the reduced than when in the oxidized form, 7 

 it may be expected that a relatively small increase in the ratio of 

 reduced to oxidized DPN may accelerate the formation of glutamic 

 acid, diminish the concentration of hepatic ammonia, and thus reduce 

 the rate of synthesis of urea. In the liver the synthesis and not the 

 oxidation of glutamic acid predominates. Accordingly, the larger pro- 

 portion of glutamic dehydrogenase is present in the reduced form and 

 is maintained in this state by the operation of DPN-dependent coupled 

 oxidations. Under conditions of low carbohydrate intake the coupling 

 of the glutamic dehydrogenase system to endogenous oxidations, prin- 

 cipally the oxidation of fat, may lead to a lower ratio of reduced to 

 oxidized DPN than that which is established in the presence of exoge- 

 nous glucose. Support for this hypothesis comes from the finding that 

 fat, unlike glucose, does not evoke nitrogen retention in adult animals 

 ingesting a protein meal. 8 If the above concept is correct, we may 

 explain the nitrogen-sparing effect of carbohydrates by assuming that, 

 in the oxidative metabolism of ingested carbohydrates, the ratio, 

 DPNH/DPN, coupled to the glutamic dehydrogenase system, is so 



